The roles of CCR6 in migration of Th17 cells and regulation of effector T-cell balance in the gut

초록

Migration and trafficking receptors of Th17 cells to mucosal tissues have been unclear. We report that Th17 cells preferentially migrate to the intestine and associated lymphoid tissues, and CCR6 is the homing receptor important for Th17 cell migration to certain tissue microenvironments of the intestine such as Peyer's patches and other sites where its ligand CCL20 is expressed. We found the cytokine transforming growth factor-beta 1 is required for CCR6 expression whereas IL-2 suppresses it. CCR6-deficient Th17 cells aberrantly migrate to different compartments of the intestine. Surprisingly, administration of CCR6-deficient Th17 cells into severe combined immunodeficiency (SCID) mice led to excessive intestinal inflammation with increased Th1 but decreased Th17 cells and FoxP3(+) T cells. In addition, CCR6 deficiency led to aberrantly widespread effector T cells in the inflamed intestine of the SCID mice. We conclude that CCR6 regulates Th17 cell migration to the gut and effector T-cell balance/distribution in inflamed intestine.

키워드